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5 results on '"Yini Xiao"'

1. Loss of ZNF148 enhances insulin secretion in human pancreatic β cells

Author

Eleonora de Klerk, Yini Xiao, Christopher H. Emfinger, Mark P. Keller, David I. Berrios, Valentina Loconte, Axel A. Ekman, Kate L. White, Rebecca L. Cardone, Richard G. Kibbey, Alan D. Attie, and Matthias Hebrok

Subjects
Metabolism, Stem cells, Medicine
Abstract

Insulin secretion from pancreatic β cells is essential to the maintenance of glucose homeostasis. Defects in this process result in diabetes. Identifying genetic regulators that impair insulin secretion is crucial for the identification of novel therapeutic targets. Here, we show that reduction of ZNF148 in human islets, and its deletion in stem cell–derived β cells (SC–β cells), enhances insulin secretion. Transcriptomics of ZNF148-deficient SC–β cells identifies increased expression of annexin and S100 genes whose proteins form tetrameric complexes involved in regulation of insulin vesicle trafficking and exocytosis. ZNF148 in SC–β cells prevents translocation of annexin A2 from the nucleus to its functional place at the cell membrane via direct repression of S100A16 expression. These findings point to ZNF148 as a regulator of annexin-S100 complexes in human β cells and suggest that suppression of ZNF148 may provide a novel therapeutic strategy to enhance insulin secretion.

Published
2023
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2. ZnT8 loss-of-function accelerates functional maturation of hESC-derived β cells and resists metabolic stress in diabetes

Author

Qing Ma, Yini Xiao, Wenjun Xu, Menghan Wang, Sheng Li, Zhihao Yang, Minglu Xu, Tengjiao Zhang, Zhen-Ning Zhang, Rui Hu, Qiang Su, Fei Yuan, Tinghui Xiao, Xuan Wang, Qing He, Jiaxu Zhao, Zheng-jun Chen, Zhejin Sheng, Mengyao Chai, Hong Wang, Weiyang Shi, Qiaolin Deng, Xin Cheng, and Weida Li

Subjects
Science
Abstract

Immature function and fragility hinder application of hESC-derived β cells (SC-β cell) for diabetes cell therapy. Here, the authors identify ZnT8 as a gene editing target to enhance the insulin secretion and cell survival under metabolic stress by abolishing zinc transport in SC-β cells.

Published
2022
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3. ZnT8 loss-of-function accelerates functional maturation of hESC-derived β cells and resists metabolic stress in diabetes

Author

Qing Ma, Yini Xiao, Wenjun Xu, Menghan Wang, Sheng Li, Zhihao Yang, Minglu Xu, Tengjiao Zhang, Zhen-Ning Zhang, Rui Hu, Qiang Su, Fei Yuan, Tinghui Xiao, Xuan Wang, Qing He, Jiaxu Zhao, Zheng-jun Chen, Zhejin Sheng, Mengyao Chai, Hong Wang, Weiyang Shi, Qiaolin Deng, Xin Cheng, and Weida Li

Subjects
Multidisciplinary, Human Embryonic Stem Cells, General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology, Mice, Zinc, Glucose, Stress, Physiological, Insulin-Secreting Cells, Diabetes Mellitus, Animals, Humans, Insulin, Cation Transport Proteins
Abstract

Human embryonic stem cell-derived β cells (SC-β cells) hold great promise for treatment of diabetes, yet how to achieve functional maturation and protect them against metabolic stresses such as glucotoxicity and lipotoxicity remains elusive. Our single-cell RNA-seq analysis reveals that ZnT8 loss of function (LOF) accelerates the functional maturation of SC-β cells. As a result, ZnT8 LOF improves glucose-stimulated insulin secretion (GSIS) by releasing the negative feedback of zinc inhibition on insulin secretion. Furthermore, we demonstrate that ZnT8 LOF mutations endow SC-β cells with resistance to lipotoxicity/glucotoxicity-triggered cell death by alleviating endoplasmic reticulum (ER) stress through modulation of zinc levels. Importantly, transplantation of SC-β cells with ZnT8 LOF into mice with preexisting diabetes significantly improves glycemia restoration and glucose tolerance. These findings highlight the beneficial effect of ZnT8 LOF on the functional maturation and survival of SC-β cells that are useful as a potential source for cell replacement therapies.

Published
2020

5. Graphene Sheet-Induced Global Maturation of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Author

Xijie Wang, Xu Ma, Jiaxian Wang, Chenchen Wang, Ellen Poon, Haiyan Nan, Yini Xiao, Yuanfang Yu, Lingsong Li, Minglong Chen, Zhenhua Ni, Kenneth R. Boheler, Gang Yang, Xin Cheng, and Chang Cui

Subjects
0301 basic medicine, Materials science, Graphene, Cardiac differentiation, Induced Pluripotent Stem Cells, Cell Differentiation, Stimulation, Nanotechnology, Biocompatible material, Regenerative medicine, In vitro, Cell biology, law.invention, 03 medical and health sciences, 030104 developmental biology, law, Humans, Regeneration, Graphite, Myocytes, Cardiac, General Materials Science, Human Induced Pluripotent Stem Cells, Myofibril
Abstract

Human induced pluripotent stem cells (hiPSCs) can proliferate infinitely. Their ability to differentiate into cardiomyocytes provides abundant sources for disease modeling, drug screening and regenerative medicine. However, hiPSC-derived cardiomyocytes (hiPSC-CMs) display a low degree of maturation and fetal-like properties. Current in vitro differentiation methods do not mimic the structural, mechanical, or physiological properties of the cardiogenesis niche. Recently, we present an efficient cardiac maturation platform that combines hiPSCs monolayer cardiac differentiation with graphene substrate, which is a biocompatible and superconductive material. The hiPSCs lines were successfully maintained on the graphene sheets and were able to differentiate into functional cardiomyocytes. This strategy markedly increased the myofibril ultrastructural organization, elevated the conduction velocity, and enhanced both the Ca2+ handling and electrophysiological properties in the absence of electrical stimulation. O...

Published
2017

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